An Investigator-Initiated Prospective Randomized Open-Label Blinded-Endpoint Crossover Trial Comparing the Effect and Safety of Flecainide and Metoprolol versus Metoprolol Alone to Suppress Ventricular Arrhythmias in Arrhythmic Mitral Valve Prolapse (FLECAPRO).

The primary objective of this study is to evaluate the **effect** and **safety** of adding **flecainide** to standard **beta blocker** therapy, specifically **metoprolol**, in reducing the burden of **ventricular arrhythmias** in patients with **arrhythmic mitral valve prolapse**. This is clinically relevant as ventricular arrhythmias can lead to significant morbidity and mortality in affected patients, and optimizing treatment regimens could improve patient outcomes.

The clinical trial involves participants diagnosed with **arrhythmic mitral valve prolapse**, aiming to assess the effect and safety of adding flecainide to standard beta blocker therapy. The study population includes both male and female subjects, aged 18 years and older, who are not considered part of a vulnerable population. Participants must have mitral valve prolapse confirmed by echocardiography or cardiac magnetic resonance imaging, with specific criteria for ventricular arrhythmias. The trial does not specify the total number of participants, as the sponsor has not provided this information. Participants are required to have a clinical indication for antiarrhythmic therapy and must adhere to contraceptive use during the trial and for a short period after discontinuation of the study medication. The selection process ensures that participants are capable of providing informed consent and complying with trial requirements. Lifestyle factors such as diet and physical activity are not detailed in the available data.

The clinical trial is designed as a **randomized**, open-label, blinded-endpoint crossover study to evaluate the effect and safety of adding **flecainide** to standard **metoprolol** therapy in patients with arrhythmic mitral valve prolapse. The trial aims to assess the reduction in ventricular arrhythmias when combining these medications compared to metoprolol alone. The study is expected to run from September 2022 to October 2025, with a maximum treatment period of 13 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, presence of mitral valve prolapse, and ventricular arrhythmias. Following successful screening, participants will be randomized to receive either the combination therapy or metoprolol alone. The trial includes multiple follow-up visits to monitor the primary endpoint, which is the number of ventricular tachyarrhythmias, and secondary endpoints such as the burden of premature ventricular complexes and health-related quality of life. The end-of-study visit will conclude the participant's involvement, assessing the overall safety and efficacy of the treatment.

Participant involvement is expected to last up to 13 weeks, with conditions for early termination including adverse events, withdrawal of consent, or non-compliance with the study protocol. The trial will ensure that all participants are informed of the requirements, including the mandatory use of contraceptive methods during the study and for three days after discontinuation of the study medication. The trial's methodology and design are structured to provide robust data on the therapeutic benefits and safety profile of the treatment regimen in the specified patient population.

The clinical trial involves the administration of **METOPROLOL**, a beta-blocker, as part of the treatment regimen. **METOPROLOL** is provided in an oral pharmaceutical form, identified by the code PHF00212MIG. The maximum daily dose of **METOPROLOL** is 200 mg, with a total maximum dose of 80,000 mg over the course of the trial. The treatment period is set for a maximum of 13 weeks. The administration route is oral, and the medication is not formulated for pediatric use. **METOPROLOL** is classified under the ATC code C07AB02 and is used as an antiarrhythmic agent in this study.

In addition to **METOPROLOL**, the trial also includes the administration of **FLECAINIDE**, another antiarrhythmic agent. **FLECAINIDE** is also administered orally, with a pharmaceutical form identified by the code PHF00209MIG. The maximum daily dose for **FLECAINIDE** is 300 mg, with a total maximum dose of 119,000 mg over the trial period. Similar to **METOPROLOL**, the treatment period for **FLECAINIDE** is also 13 weeks. **FLECAINIDE** is classified under the ATC code C01BC04. The trial aims to evaluate the effect and safety of adding **FLECAINIDE** to standard beta-blocker therapy to reduce the burden of ventricular arrhythmias in patients with arrhythmic mitral valve prolapse.

Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed treatment regimen. The trial is designed as an open-label, blinded-endpoint crossover study, allowing for a comprehensive assessment of the therapeutic effects and safety profile of the combined treatment versus **METOPROLOL** alone.

Efficacy in the clinical trial titled "An Investigator-Initiated Prospective Randomized Open-Label Blinded-Endpoint Crossover Trial Comparing the Effect and Safety of Flecainide and Metoprolol versus Metoprolol Alone to Suppress Ventricular Arrhythmias in Arrhythmic Mitral Valve Prolapse (FLECAPRO)" will be assessed using specific primary and secondary endpoints. The primary endpoint is the number of ventricular **tachyarrhythmias**, which is a composite measure including ventricular tachycardia and ventricular fibrillation. Secondary endpoints include the burden of premature ventricular complexes as measured by 24-hour Holter monitoring, health-related quality of life indicated by a ≥5 points increase in the SF-36 overall summary score, and the number of severe ventricular tachycardias, which is a composite of non-sustained ventricular tachycardia with syncope, sustained ventricular tachycardia, and ventricular fibrillation.

The trial aims to evaluate the effect and safety of adding flecainide to standard beta blocker therapy in reducing the burden of ventricular arrhythmias in patients with arrhythmic mitral valve prolapse. The efficacy parameters will be collected and analyzed at specified timepoints throughout the trial duration, which is estimated to end on October 31, 2025. The trial involves the use of antiarrhythmic medications, specifically **metoprolol** and **flecainide**, administered orally. The maximum treatment period for the medications is 13 weeks. The trial is not categorized as low intervention and is conducted under a phase 5 trial category, focusing on the efficacy and safety of existing investigational medicinal products for indications other than those currently authorized.